Identification of therapeutic targets for treatment of intermittent claudication that mimic the effects of exercise

Exercise is considered as the most efficacious intervention for improving walking capacity in patients with intermittent claudication (IC). Despite its benefits, the underlying mechanisms inducing this effect remain unclear. To elucidate the local mechanisms in skeletal muscle, we previously developed an electrical stimulating (ES) model which caused skeletal muscle contraction mimicking exercise. ES showed the improvement in walking ability in rat IC model. In this study, we compared gene expressions among hindlimb ischemia (Isch) group, Isch + exercise group, and Isch + ES group in rat using GeneChip analysis and real-time PCR. By extracting genes which were similarly altered in both exercise and ES groups compared with Isch group, we revealed candidate genes that might be involved in improvement of walking ability. In order to investigate the effects of skeletal muscle contraction against IC symptom, we developed electrical stimulation (ES) system in rat IC model. ES could improve walking performance in the rat claudication model as well as exercise. We postulated that nerve-mediated skeletal muscle contraction, which caused by both ES and exercise would affect ischemic hindlimbs directly and the changes contributed to improve walking distance in rat IC model. In order to obtain a comprehensive understanding of the mechanisms of exercise and ES, changes of expressions by exercise and ES versus ischemic group in rat skeletal muscle were analyzed.